
Welcome. 
So, today we want to continue our 
discussion of the inter consistent, the 
general concepts of the inter 
consistence, and today we want to talk 
about two specific things. 
That is the, the assessment of these 
systems and its pathology. 
That, the way you classify the pathology. 
So first we want to explain then the 
principles and limitations of how we 
measure the hormones. 
the, and this is done in 2 ways. 
One is by actually quantitating them and 
secondly, asking whether or not they're 
active. 
And then secondly, we want to explain the 
classification of this endocrine 
pathologies. 
So assessment of function. 
So as we said last time we were here that 
if we have too much hormone that we have, 
that we have a hyper secretion of the 
hormone. 
We have hormone excess. 
And the problem with this situation is is 
that you can have down regulation of the 
target cell receptor. 
We could desensitize the system so that 
it's not recognizing, it's not giving us 
the biological activity. 
Or we can have a really, really strong 
response, and so we have an over response 
to the amount of hormones that's being 
available. 
The second was that we have too little 
concentration of the hormone, we have 
hypo-secretion of the hormone. 
And this would be hormone insufficiency, 
where not enough of the receptors on the 
target cells are, are occupied and we 
don't get the biological effect that we, 
that we need, or the biological response 
that we need. 
And then we said, we can also have target 
cell resistance and this is a problem 
whether receptors on the target cells are 
unresponsive and they could be 
unresponsive because they are uncoupled. 
So they are still present on their cell 
surface. 
This is what we see with Diabetes type 2 
individuals often. 
Where we have the receptors actually 
removed or degraded and so its not even 
present on the, on the cell surface. 
And then just right is a normal or 
eu-secretion and that's where the hormone 
system, the endocrine system, is working 
correctly. 
So we have two assays for, for measure 
our hormones and one of them is called 
competitive binding assay. 
Remember that the hormones are very, very 
concentrations within the blood. 
So we have to have this a, a, very 
sensitive assay to find the amount of 
hormone that's within our sample. 
And to do this we use a specific 
antibody. 
So this antibody then recognizes the 
hormone in hmm, and we have in our system 
in the, in the as a, we put in labeled 
hormones we have a a known amount of 
labeled hormone. 
That will bind up all of the antibody 
that's within the system. 
We mix this with an hormone that's from 
our patient or from our, the unknown, 
that's, we don't know the amount of 
hormone that's here, so this our X 
amount. 
And we mix this then with the Knownr or 
labeled hormone and/or antibody, and 
then, then assay for how much of the 
hormone, the labeled hormone, has been 
brought down. 
And the unlabeled hormone should compete 
a finite amount of the labeeled hormone 
and then we by subtraction. 
We can, we know how much should have come 
down, by subtraction we can figure out 
how much of the unlabeled hormone we have 
present in the sample. 
So this is high sen, sensitivity because 
of the antibodies and its high 
specificity because of the antibody. 
But it doesn't tell you if the hormone 
is, is active. 
So when could, when could this give us a 
false reading? 
So, let's say you have an individual who 
presents as if they are diabetic type 
one. 
These individuals have very high 
circulating levels of plasma and glucose. 
They have high, high circulating levels 
of plasma glucose. 
But when you assay for the insulin in 
their, in their bloodstream. 
You find that insulin is also present. 
So, by this competitive binding assay, 
the insulin is present. 
So the question is, is the insulin that 
they're making functional. 
So the way you test that would be that 
you would give this individual some 
insulin that you know is functional and 
see whether or not the amount of glucose 
is circulating in the plasma will 
decrease. 
If it does then you know, that the, that 
the insulin that the individual's making 
is making an insulin that's not reactive, 
it cannot bind to the receptor or it has 
some problem in it's, in it's structure. 
So we have to have a second assay then 
which tells us whether or not our hormone 
is functional. 
These are called bioassays. 
So what I've diagramed here is a complex 
complex negative feedback loop of one of 
the hormones that we'll talk about later 
on in the course. 
But this particular hormone is cortisol 
and it is secreted by the adrenal gland. 
This hormone is secreted in response to a 
low plasma glucose. 
So we have low plasma glucose than the 
hypothalamus, which is the area of your 
brain will secrete a hormone called CRH 
or corticotropin. 
This hormone binds with the second area 
of a brain called the anterior pituitary 
to secrete. 
ACTH, adrenal corticalthrophin. 
This hormone works on the adrenal cortex 
to cause the secretion of cortisol. 
So that's our regular stimulation of the 
cortisol from the adrenal gland. 
Cortisol happens to be a steroid hormone 
so it takes about 30 to 60 minutes before 
cortisol will rise in the blood. 
And the reason for the delay is that 
cortisol is, is, is a steroid derivative, 
so it has to be synthesized on demand. 
And then cortisol is secreted into the 
blood and delivered by, by its carrier 
and then it's delivered to its target 
target tissue. 
The cortisol will feed back in a negative 
manner to turn off secretion from the 
interior pituitary and from the 
hypothalamus. 
And this is a complex negative feedback 
loops that we saw when we were talking 
about homeostatic controls in the first 
lecture. 
So what happens if the cortisol that's in 
the particular individual is very, very 
high? 
So we have very high levels of, of of 
cortisol. 
And because we have high levels of 
cortisol, we will actualy have very high 
levels of plasma glucose. 
And the individual is coming into the 
physician's office because of the 
symptoms that this very high cortisol is 
causing within his body. 
So this high cortisol should have fed 
back and turned off ACTH and turned off 
CRH. 
But it doesn't seem to be is too high. 
So, the question is, do we have a tumor 
that's making this cortisol or do we have 
too much of this ACTH, which is pushing 
the synthesis of the cortisol. 
So, is the problem occurring here, at the 
ACTH level, or is the problem occurring 
here, at the, at the cortisol level, at 
the adrenal, itself. 
So to test this axis then we run a 
supression test and this is that we give 
a drug called dexamethasone which 
inhibits the synthasis of ACTH by 
patuitary cells. 
When we get this drug if we adminster the 
drug the ACTH levels shoudl fall. 
And when the ACTH level should fall, then 
the cortisol levels should also fall. 
So if we had a very high amount if ACTH, 
then we turn off the ACTH, the cortisol 
should fall. 
If the cortisol does not fall under these 
conditions. 
Then the, the question is, is whether or 
not the ACTH has gone down. 
And you can then assay for the ACTH. 
If on the other hand the cortisol does 
fall and, and the ACTH, let's say the 
ACTH under those circumstances did fall. 
But that the cortisol stayed high, that 
would tell you that there's a problem 
with the adrenal gland, or that theres a 
problem with a tumor someplace in the 
body that secreting cortisol. 
It's not under the regulation of ACTH. 
So, this is a way then that we can sort 
of, parse the axis to find out exactly 
where in the axis our problem lies. 
Let's look at a case where we have the 
opposite, where we have low cortisol, we 
have low cortisol levels. 
The hypothalamus secretes CRH due to the 
low plasma glucose And we should have a 
ACTH but we have low cortisol. 
We can get this individual ACTH so 
exonginous ACTH to push the axis to see 
whether or not the adrenal is working. 
And when we do that the cortisol levels 
should rise. 
We wait 30 to 60 minutes, and we should 
see rise in cortisol levels. 
If the gland, the adrenal gland, is 
working correctly then the exogenous ACTH 
should correct the situation, we should 
see rise in cortisol. 
That things tells us that there was a 
problem with the anterior pituitary, that 
it was not secreting ACTH correctly or 
they may have been a problem with the CRH 
which is then there was a decrease in the 
ACTH. 
So that level then have to go back and 
look whether ACTH and CRH levels are 
appropriate. 
So how do you classify these endocrine 
pathologies? 
So the endocrine pathologies then, in the 
situation where we have this complex 
negative feedback loop, we have a primary 
pathology if the last endocrine organ is 
not working correctly. 
So in our case we have low cortisol And 
that endrocrine organ was teh adrenal 
cortex. 
If we have a low cortisol what we should 
have seen if the problem is sitting here. 
Then we should have seen is that ACTH 
levels would be high and CRH levels would 
be high if the system would be trying to 
push to get an increase in the cortisol. 
On the other and we don't have a negative 
feedback loop to decrease the ACTH or the 
CRH because the cortisol level is low. 
If the problem was secondary, then we'd 
have a low cortisol but we'd also have a 
low ACTH the ACTH is the problem and that 
means if the problem is setting here at 
the pituitary. 
This CRH then could be high because the 
CRH is trying to push the ACTH but the 
ACTH is not being secreted correctly. 
It's low so therefor cortisol is low. 
That will be classifed as a secondary 
pathology. 
And if the problem is occurring at the 
level of the hypothalamus then this is a 
tertiary problem where we have low 
cortisol, we have low ACTH, we have low 
CRH, and the entire axis is down 
regulated. 
When the entire axis is down regulated, 
we are missing the CRH in this [UNKNOWN] 
individuals, then the individual can be 
given ACTH. 
By giving them ACTH we then can move the 
cortisol levels up, because the adrenal 
gland was working correctly. 
So these pathologies then, as you're 
looking through, these different problems 
and we want to see whether or not what 
these different pathologies are. 
And to be able to classify at what level 
the pathology is occurring. 
This is a misspelling. 
Alright so what of our general concepts 
then? 
The patholi-, first of all we have 
pathology and endocrinology occurs when 
there is either too little or too much 
hormone. 
Or we have a resistance to the hormone 
due to receptor disfunction. 
And secondly we can interpret the hormone 
levels in and as we're interpreting the 
hormone levels we have to consider the 
trophic hormones that are above it and/or 
the level of the nutrients which are 
controlled by the hormone. 
So in the case of a more complex negative 
feedback loop we have to consider all of 
the hormones which are within that 
negative feedback loop as to whether or 
not they may be the problem. 
And you start with the primary and then, 
and then work backwards. 
But you have assays where you can assay 
the amount of, for instance, we could 
assay the amount of ACTH, we could assay 
the amount of cortisol But you start with 
asking the amount of choritisol and then 
go back and see whether or not there was 
a problem with the HCTH. 
So I hope this makes sense to everybody 
you should go ahead and try the, the 
problem sets because this will allow you 
to apply what you've learned from these 
various concepts in endocrinology. 
to two actual cases and see whether or 
not you can think through these cases. 
Okay, so see you next, bye bye. 

